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ENeuro Jun 2024Ghrelin is a stomach-derived hormone that increases feeding and is elevated in response to chronic psychosocial stressors. The effects of ghrelin on feeding are mediated...
Ghrelin is a stomach-derived hormone that increases feeding and is elevated in response to chronic psychosocial stressors. The effects of ghrelin on feeding are mediated by the binding of ghrelin to the growth hormone secretagogue receptor (GHSR), a receptor located in hypothalamic and extra-hypothalamic regions important for regulating food intake and metabolic rate. The ability of ghrelin to enter the brain, however, seems to be restricted to circumventricular organs like the median eminence and the brain stem area postrema (AP), whereas ghrelin does not readily enter other GHSR expressing regions like the ventral tegmental area (VTA). Interestingly, social stressors result in increased blood brain barrier permeability, and this could therefore facilitate the entry of ghrelin into the brain. To investigate this, we exposed mice to social defeat stress for 21 days, then peripherally injected a Cy5-labelled biologically active ghrelin analogue. Results demonstrate that chronically stressed mice exhibit higher Cy5-ghrelin fluorescence in several hypothalamic regions in addition to the ARC, including the hippocampus and midbrain. Furthermore, Cy5-ghrelin injections resulted in increased FOS expression in regions associated with the reward system in the chronically stressed mice. Further histologic analyses identified a reduction in branching of hypothalamic astrocytes in the ARC-median eminence junction, suggesting increased blood-brain barrier permeability. These data support the hypothesis that during metabolically challenging conditions like chronic stress, ghrelin may be more able to cross the blood brain barrier and diffuse throughout the brain to target GHSR expressing brain regions away from circumventricular organs. Ghrelin is secreted in response to negative energy balance states including stress and is associated with changes in food intake and energy balance. The receptors for ghrelin are found throughout the brain but ghrelin seems to only reach circumventricular regions where the blood brain barrier is more porous. In this paper we demonstrate that chronic social defeat stress increases brain permeability to ghrelin to allow for entry and activation of target sites in the mesolimbic dopaminergic system that are not accessible to ghrelin under non-stress conditions. Overall, these results provide for an explanation as to how ghrelin can access the mesolimbic dopaminergic system in a state dependent manner.
PubMed: 38937108
DOI: 10.1523/ENEURO.0093-24.2024 -
The Journal of Neuroscience : the... Jun 2024The encoding of acoustic stimuli requires precise neuron timing. Auditory neurons in the cochlear nucleus (CN) and brainstem are well-suited for accurate analysis of...
The encoding of acoustic stimuli requires precise neuron timing. Auditory neurons in the cochlear nucleus (CN) and brainstem are well-suited for accurate analysis of fast acoustic signals, given their physiological specializations of fast membrane time constants, fast axonal conduction, and reliable synaptic transmission. The medial olivocochlear (MOC) neurons that provide efferent inhibition of the cochlea reside in the ventral brainstem and participate in these fast neural circuits. However, their modulation of cochlear function occurs over time scales of a slower nature. This suggests the presence of mechanisms that reduce MOC inhibition of cochlear function. To determine how monaural excitatory and inhibitory synaptic inputs integrate to affect the timing of MOC neuron activity, we developed a novel in vitro slice preparation ('wedge-slice'). The wedge-slice maintains the ascending auditory nerve root, the entire CN and projecting axons, while preserving the ability to perform visually guided patch-clamp electrophysiology recordings from genetically identified MOC neurons. The 'in vivo-like' timing of the wedge-slice demonstrates that the inhibitory pathway accelerates relative to the excitatory pathway when the ascending circuit is intact, and the CN portion of the inhibitory circuit is precise enough to compensate for reduced precision in later synapses. When combined with machine learning PSC analysis and computational modeling, we demonstrate a larger suppression of MOC neuron activity when the inhibition occurs with in vivo-like timing. This delay of MOC activity may ensure that the MOC system is only engaged by sustained background sounds, preventing a maladaptive hyper-suppression of cochlear activity. Auditory brainstem neurons are specialized for speed and fidelity to encode rapid features of sound. Extremely fast inhibition contributes to precise brainstem sound encoding. This circuit also projects to medial olivocochlear (MOC) efferent neurons that suppress cochlear function to enhance detection of signals in background sound. Using a novel brain slice preparation with intact ascending circuitry, we show that inhibition of MOC neurons can also be extremely fast, with the speed of the circuit localized to the cochlear nucleus. In contrast with the enhancement of precision afforded by fast inhibition in other brainstem auditory circuits, inhibition to MOC neurons instead has a variable onset that delays and desynchronizes activity, thus reducing precision for a slow, sustained response to background sounds.
PubMed: 38937103
DOI: 10.1523/JNEUROSCI.0382-24.2024 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024Even partly consolidated memories can be forgotten given sufficient time, but the brain activity associated with durability of episodic memory at different time scales...
Even partly consolidated memories can be forgotten given sufficient time, but the brain activity associated with durability of episodic memory at different time scales remains unclear. Here, we aimed to identify brain activity associated with retrieval of partly consolidated episodic memories that continued to be remembered in the future. Forty-nine younger (20 to 38 years; 25 females) and 43 older adults (60 to 80 years, 25 females) were scanned with functional magnetic resonance imaging during associative memory retrieval 12 h post-encoding. Twelve hours is sufficient to allow short-term synaptic consolidation as well as early post-encoding replay to initiate memory consolidation. Successful memory trials were classified into durable and transient source memories based on responses from a memory test ~6 d post-encoding. Results demonstrated that successful retrieval of future durable vs. transient memories was supported by increased activity in a medial prefrontal and ventral parietal area. Individual differences in activation as well as the subjective vividness of memories during encoding were positively related to individual differences in memory performance after 6 d. The results point to a unique and novel aspect of brain activity supporting long-term memory, in that activity during retrieval of memories even after 12 h of consolidation contains information about potential for long-term durability.
Topics: Humans; Female; Male; Adult; Magnetic Resonance Imaging; Middle Aged; Young Adult; Mental Recall; Aged; Memory, Episodic; Memory Consolidation; Aged, 80 and over; Brain; Brain Mapping; Time Factors
PubMed: 38937077
DOI: 10.1093/cercor/bhae233 -
Parasitology International Jun 2024A new genus, Cordicestus, is proposed to accommodate proteocephalid tapeworms parasitising gars (Lepisosteiformes: Lepisosteidae) in North and Central America that were...
A new genus, Cordicestus, is proposed to accommodate proteocephalid tapeworms parasitising gars (Lepisosteiformes: Lepisosteidae) in North and Central America that were previously placed in the polyphyletic genus Proteocephalus Weinland, 1858. The new genus differs from other proteocephalid genera by the particular morphology of the scolex, which is small, protrudes apically but has no apical organ, and bears flat, heart-shaped (= cordis) suckers. In addition, the species of the new genus have an elongated cirrus sac with an almost straight internal vas deferens, and wide, sinuous ventral osmoregulatory canals with secondary canals directed outwards. The type species of the new genus, Cordicestus singularis (La Rue, 1911) n. comb., is redescribed based on new material from the shortnose gar, Lepisosteus platostomus Rafinesque (type host), and the spotted gar, L. oculatus Winchell, in the United States. Cordicestus rafaeli n. sp. is described from the tropical gar, Atractosteus tropicus Gill, in Mexico. The new species differs from its relatives primarily by the presence of craspedote proglottids (acraspedote in other species) and some biometric features. The species of Cordicestus are discussed, including unidentified specimens from A. tropicus and the Cuban gar A. tristoechus (Bloch and Schneider) in Nicaragua and Cuba, respectively, which may be new species, and a key to identification of these taxa is provided. Molecular data available for two nominal species of the new genus indicate the possible existence of another species of Cordicestus in Lepisosteus in the USA.
PubMed: 38936764
DOI: 10.1016/j.parint.2024.102916 -
Current Biology : CB Jun 2024Predictive learning can engage a selective form of cognitive control that biases choice between actions based on information about future outcomes that the learning...
Predictive learning can engage a selective form of cognitive control that biases choice between actions based on information about future outcomes that the learning provides. This influence has been hypothesized to depend on a feedback circuit in the brain through which the basal ganglia modulate activity in the prefrontal cortex; however, direct evidence for this functional circuit has proven elusive. Here, using an animal model of cognitive control, we found that the influence of predictive learning on decision making is mediated by an inhibitory feedback circuit linking the medial ventral pallidum and the mediodorsal thalamus, the activation of which causes disinhibition of the orbitofrontal cortex via reduced activation of inhibitory parvalbumin interneurons during choice. Thus, we found that, for this function, the mediodorsal thalamus serves as a pallidal-cortical relay through which predictive learning controls action selection, which has important implications for understanding cognitive control and its vicissitudes in various psychiatric disorders and addiction.
PubMed: 38936365
DOI: 10.1016/j.cub.2024.06.011 -
Zoology (Jena, Germany) Jun 2024Disproportional changes (i.e. allometry) in shark morphology relative to increasing body size have been attributed to shifts in function associated with niche shifts in...
Disproportional changes (i.e. allometry) in shark morphology relative to increasing body size have been attributed to shifts in function associated with niche shifts in life history, such as in habitat and diet. Photographs of blue sharks (Prionace glauca, 26-145 kg) were used to analyze changes in parameters of body and fin morphology with increasing mass that are fundamental to swimming and feeding. We hypothesized that blue sharks would demonstrate proportional changes (i.e. isometry) in morphology with increasing mass because they do not undergo profound changes in prey and habitat type; accordingly, due to geometric scaling laws, we predicted that blue sharks would grow into bodies with greater turning inertias and smaller frontal and surface areas, in addition to smaller spans and areas of the fins relative to mass, which are parameters that are associated with the swimming performance in sharks. Many aspects of morphology increased with isometry. However, blue sharks demonstrated negative allometry in body density, whereas surface area, volume and roll inertia of the body, area, span and aspect ratio of both dorsal fins, span and aspect ratio of the ventral caudal fin, and span, length and area of the mouth increased with positive allometry. The dataset was divided in half based on mass to form two groups: smaller and larger sharks. Besides area of both dorsal fins, relative to mass, larger sharks had bodies with significantly greater turning inertia and smaller frontal and surface areas, in addition to fins with smaller spans and areas, compared to smaller sharks. In conclusion, isometric scaling does not necessarily imply functional similarity, and allometric scaling may sometimes be critical in maintaining, rather than shifting, function relative to mass in animals that swim through the water column.
PubMed: 38936326
DOI: 10.1016/j.zool.2024.126184 -
Developmental Cognitive Neuroscience Jun 2024Adolescent risk-taking has been attributed to earlier-developing motivational neurocircuitry that is poorly controlled by immature executive-control neurocircuitry....
Adolescent risk-taking has been attributed to earlier-developing motivational neurocircuitry that is poorly controlled by immature executive-control neurocircuitry. Functional magnetic resonance imaging findings of increased ventral striatum (VS) recruitment by reward prospects in adolescents compared to adults support this theory. Other studies found blunted VS recruitment by reward-predictive cues in adolescents compared to adults. Task features may explain this discrepancy but have never been systematically explored. Adolescents and adults performed a novel reward task that holds constant the expected value of all rewards but varies whether rewards are dependent on vigilance-intensive responding versus making a lucky choice during a relaxed response window. We examined group by sub-task contrast differences in activation of VS and more motoric regions of striatum in response to anticipatory cues. Reward anticipation in both task conditions activated portions of striatum in both groups. In voxel-wise comparison, adults showed greater anticipatory recruitment of VS in trials involving choice during a relaxed time window, not in the more vigilance-demanding trials as hypothesized. In accord with our hypotheses, however, adults showed greater activation in dorsal striatum and putamen volumes of interest during reward anticipation under vigilance-demanding conditions. Following trial outcome notifications, adolescents showed greater activation of the VS during reward notification but lower activation during loss notification. These data extend findings of cross-sectional age-group differences in incentive-anticipatory recruitment of striatum, by demonstrating in adults relatively greater recruitment of motor effector regions of striatum by attentional and motor demands.
PubMed: 38936253
DOI: 10.1016/j.dcn.2024.101412 -
Neural Networks : the Official Journal... Jun 2024Our minds represent miscellaneous objects in the physical world metaphorically in an abstract and complex high-dimensional object space, which is implemented in a...
Our minds represent miscellaneous objects in the physical world metaphorically in an abstract and complex high-dimensional object space, which is implemented in a two-dimensional surface of the ventral temporal cortex (VTC) with topologically organized object selectivity. Here we investigated principles guiding the topographical organization of object selectivities in the VTC by constructing a hybrid Self-Organizing Map (SOM) model that harnesses a biologically inspired algorithm of wiring cost minimization and adheres to the constraints of the lateral wiring span of human VTC neurons. In a series of in silico experiments with functional brain neuroimaging and neurophysiological single-unit data from humans and non-human primates, the VTC-SOM predicted the topographical structure of fine-scale category-selective regions (face-, tool-, body-, and place-selective regions) and the boundary in large-scale abstract functional maps (animate vs. inanimate, real-word small-size vs. big-size, central vs. peripheral), with no significant loss in functionality (e.g., categorical selectivity and view-invariant representations). In addition, when the same principle was applied to V1 orientation preferences, a pinwheel-like topology emerged, suggesting the model's broad applicability. In summary, our study illustrates that the simple principle of wiring cost minimization, coupled with the appropriate biological constraint of lateral wiring span, is able to implement the high-dimensional object space in a two-dimensional cortical surface.
PubMed: 38936111
DOI: 10.1016/j.neunet.2024.106437 -
Hernia : the Journal of Hernias and... Jun 2024Spigelian hernias are among the rare primary ventral hernias. Diagnosis is often difficult, as many cases are asymptomatic. Spigelian and inguinal hernias are usually...
INTRODUCTION
Spigelian hernias are among the rare primary ventral hernias. Diagnosis is often difficult, as many cases are asymptomatic. Spigelian and inguinal hernias are usually considered separately in current scientific literature. With this case series, we want to illustrate a possible relationship between the neighboring hernia types.
METHODS
In this article, we report on a case series of Spigelian hernias that were operated on in five hernia centers in the period from January 1st, 2021 to October 31st, 2023. We have summarized all patient characteristics with previous operations and the result of the secondary operation.
RESULTS
We report a case series with 24 Spigelian hernias, 15 of which have a connection to previous inguinal hernias. In these cases, however, it is not certain whether these are primarily overlooked or occult hernias or whether these Spigelian hernias have arisen secondarily, as a result of previous hernia surgery. With this case series, we would like to point out a possible connection between Spigelian hernia and inguinal hernia. Further studies are needed to shed more light on this entity and explain its genesis.
PubMed: 38935190
DOI: 10.1007/s10029-024-03061-5 -
Archives of Dermatological Research Jun 2024Current strategies for hypertrophic scar prevention and treatment are limited.
BACKGROUND
Current strategies for hypertrophic scar prevention and treatment are limited.
OBJECTIVE
To facilitate these efforts, a minimally invasive hypertrophic scar model was created in a rabbit ear for the first time based on previous methods used to induce ischemia.
METHODS
Six New Zealand white rabbits (12 ears total) were studied. First, ischemia was achieved by ligating the cranial artery, cranial vein and central artery, while preserving the caudal artery, caudal vein and central vein, respectively. The relative level of ischemia induced at time of surgery, both baseline and maximum perfusion, was assessed with a fluorescent light-assisted angiography and demonstrated lower rates of perfusion in the ischemic ears. Following vascular injury, a 2-cm full thickness linear wound was created on the ventral ear and closed with 4 - 0 Nylon sutures under high tension. For each rabbit, one ear received a combination of ischemia and wounding with suture tension (n = 6), while the other ear was non-ischemic with wounding and suture tension alone (n = 6).
RESULTS
Four weeks post-operatively, ischemic ears developed scar hypertrophy (histological scar thickness: 1.1 ± 0.2 mm versus 0.5 ± 0.1 mm, p < 0.05).
CONCLUSION
Herein, we describe a novel, prototypical minimally invasive rabbit ear model of hypertrophic scar formation that can allow investigation of new drugs for scar prevention.
Topics: Animals; Rabbits; Cicatrix, Hypertrophic; Disease Models, Animal; Minimally Invasive Surgical Procedures; Ear; Ischemia; Humans; Wound Healing; Suture Techniques
PubMed: 38935157
DOI: 10.1007/s00403-024-03185-9